Sustained β-adrenergic stimulation increased L-type Ca2+ channel expression in cultured quiescent ventricular myocytes
Sustained β-adrenergic stimulation increased L-type Ca2+ channel expression in cultured quiescent ventricular myocytes
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DOI：
10.2170/physiolsci.rp001406
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发表时间：
2006-04-01
影响因子：
2.3
通讯作者：
Ochi, Rikuo
中科院分区：
文献类型：
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作者：
Akuzawa-Tateyama, Miyuki;Tateyama, Michihiro;Ochi, Rikuo
β-肾上腺素能受体（β-AR）刺激和心肌细胞内Ca2+浓度升高改变了电压门控L型Ca2+通道的丰度。在整体动物中，慢性β-AR刺激或心脏起搏导致通道丰度的各种变化，但它降低了L-型通道的β-AR反应性。由于β-AR刺激促进L-型钙通道，很难在整个动物中研究β-AR和Ca~（2+）内流对L-型通道上调的相互独立的作用，这使得无搏动的成人心肌细胞的培养成为一个有吸引力的模型。我们发现，培养静止的成年兔心室肌细胞与异丙肾上腺素（ISO，2 μ m）为72小时或更长的时间引起的mRNA编码的L型通道α（1C）亚基的表达显着增加约2倍，与时间匹配的对照组相比，其次是在96小时的钙电流密度增加1.8倍。有些令人惊讶的是，急性应用1 μ m ISO增加了电流幅度，即使在ISO处理的细胞。由持续的P-AR刺激引起的电流密度的增加被β-AR拮抗剂普萘洛尔（10 μ m）阻断，但不被Ca 2+拮抗剂尼群地平（10 μ m）阻断。此外，毛喉素（10 μ m），但不是由Ca2+激动剂，Bay-K 8644（2 μ m）再现的效果。总之，这些结果表明，持续β-AR刺激上调L型通道的表达，但不改变静止心肌细胞中通道的P-AR反应性。
The abundance of voltage-gated L-type Ca2+ channels is altered by P-adrenergic receptor (beta-AR) stimulation and by an elevation of the intracellular Ca2+ concentration in cardiac myocytes. In whole animal, chronic beta-AR stimulation or pacing heart results in various changes in the abundance of the channel, but it reduces the beta-AR responsiveness of the L-type channel. Because beta-AR stimulation facilitates the L-type calcium channels, it is difficult in the whole animal to study the effects of beta-AR and Ca2+ influx on the upregulation of the L-type channel independently of each other, which makes the cultur of nonbeating adult myocytes an attractive model. We found that culturing quiescent adult rabbit ventricular myocytes with isoproterenol (ISO, 2 mu m) for 72 h or more caused a significant increase in the expression of mRNA coding for the L-type channel alpha(1C) subunit by approximately twofold as compared to time-matched controls, and it was followed by a 1.8-fold increase in the Ca2+ current density at 96 h. Somewhat surprisingly, an acute application of 1 mu m ISO increased the current amplitude even in ISO-treated cells. The increase in the current density, induced by sustained P-AR stimulation, was blocked by a beta-AR antagonist, propranolol (10 mu m), but not by a Ca2+ antagonist, nitrendipine (10 mu m). In addition, the effects were reproduced by forskolin (10 mu m), but not by a Ca2+ agonist, Bay-K 8644 (2 mu m). Taken together, these results suggest that sustained beta-AR stimulation upregulates L-type channel expression, but does not alter the P-AR responsiveness of the channel in quiescent myocytes.